Cancer of the prostate is the most commonly diagnosed cancer in man and is the second most common cause of cancer death ((1) American Cancer Society, Cancer Facts & Figures, 2003; (2) Carter, H. B. and Coffey, D. S. (1990) Prostate 16:39-48; (3) Armbruster, D. A. (1993) Clin Chem 39:181-195). If detected at an early stage, prostate cancer is potentially curable. However, a majority of cases are diagnosed at later stages when metastasis of the primary tumor has already occurred (Wang, M. C., Kuriyama, M., Papsidero, L. D., Loor, R. M., Valenzuela, L. A., Murphy, G. P., and Chu, T. M. (1982) Methods in Cancer Research 19:179-197). Present treatments for prostate cancer include radical prostatectomy, radiation therapy, or hormonal therapy. No systemic therapy has clearly improved survival in cases of hormone refractory disease. With surgical intervention, complete eradication of the tumor is not always achieved and the observed reoccurrence of the cancer (12-68%) is dependent upon the initial clinical tumor stage (Zietman, A. L., Shipley, W. L., and Willett, C. G. (1993) Cancer 71:959-969). Thus, alternative methods of treatment including prophylaxis or prevention are desirable.
Over the last decade, diagnostic tools for prostate cancer (PCa) have improved tremendously with the use of prostate specific antigen (PSA) as a marker for the disease. PSA is a 28 kDa glycoprotein secreted by the prostatic epithelium. It consists of 237 amino acids and approximately 8% carbohydrate N-linked to the peptide backbone through an asparagine (Asn, N) residue1, and exists in several natural isoforms2,3. Serum levels of PSA in its various bound (e.g., PSA-α1-antichymotrypsin, or PSA-ACT) and free (f-PSA and pro-PSA3) states are currently used as markers for the diagnosis of prostate cancer,4-13 but immunoassays based on PSA concentration alone do not clearly distinguish between benign prostatic hyperplasia (BPH) and prostate cancer. PSA-based assays originally measured gross serum levels14,15 of total PSA (t-PSA) and yielded an ambiguous diagnosis for PCa or BPH at concentrations ranging from 4 to 10 μg/L. Improved accuracy in this range is reportedly achieved using serum level comparisons of f-PSA and t-PSA known as the PSA index, but the utility of such immunoassays is debatable.16-19 Another method for diagnosis based on serum PSA content, called PSA velocity, involves monitoring increased PSA levels over time for a particular patient.20,21 Though free from the dependence upon average values for expected PSA concentrations in healthy, BPH, and PCa patients, such diagnostics place considerable demands on assay stability and consistency over time.16 
Thus prostate cancer diagnosis would benefit from a new, more accurate immunoassay. To this end, we note that differentially expressed N-linked carbohydrates have been associated with the onset or metastasis of several cancers,22 including breast,23,24 colon,23 and lung25 cancers. Carbohydrates from normal PSA are reportedly biantennary N-linked glycans (see structure below) terminated in variable numbers of sialic acid residues.26,27

However, a recent study indicates that PSA from a metastatic prostate cell line (LnCaP) also exhibits larger, more highly branched carbohydrates of the type illustrated in the boxed structure of Scheme 1, though the altered glycans were not isolated and their precise structures are yet to be determined.28 It has been suggested that the differentially glycosylated region of transformed PSA could be used as a molecular marker specific for PCa over BPH.27,28 To study this issue in detail requires pure, homogeneous PSA glycopeptides; however, useful samples of homogeneous glycosylated PSA from natural sources are prohibitively difficult to obtain. Furthermore, purified PSA displays several glycoforms upon hydrazinolytic cleavage.27 Obtaining homogeneous samples of PSA glycopeptides thus requires a source of homogeneous carbohydrates and a chemoselective method for construction of the glycosylated peptide.
Accordingly, there remains a need for novel synthetic methods leading to the preparation of normal and transformed PSA glycans and conjugates thereof, and their evaluation in immunologic and therapeutic studies.